JAX®In Vivo Xenograft Services

JAX® NOTES Issue 508, Winter 2008

JAX®In Vivo Services performs a variety of flexible and customizable services using mouse models. One of these, the Xenograft Service, assesses the efficacy of anti-cancer drugs on the rate of staged, subcutaneous engrafted tumor growth in mouse models. Every clinically approved agent for treating cancer has shown activity in conventional preclinical in vivo models (Sausville and Burger 2006). The most accessible, efficient, and genetically well-characterized model organism for xenotransplantation is the mouse. A sample study protocol for the JAX®In Vivo Xenograft Service is outlined below.

Basic Study Design

Mice from an immune compromised strain (Table 1) are transferred to our In Vivo Services facility, where they are housed at up to 5 per cage with ad libitum access to standard chow and water.

Table 1. Some JAX® Mice strains commonly used as xenograft models.

Name

Common Name

Stock Number

NOD.CB17-Prkdcscid/J

NOD scid

001303

CBySmn.CB17-Prkdcscid/J

BALB scid

001803

NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ

IL2rg null

005557

B6.129S7-Rag1tm1Mom/J

Rag1 null

002216

NU/J

nu/nu

002019

After acclimating to these conditions for a week, the mice are subcutaneously injected in the flank with tumor cells. Currently, we maintain more than 22 human tumor cell lines (Table 2), but we can also use additional commercial cell lines and customer-provided lines. The tumor site is palpated up to 3 times weekly until the tumor is established. Once the tumor is sufficiently large, the mice are stratified by tumor size and randomly assigned to various cohorts. Cohorts are dosed with a compound, according to a route and schedule of your choice. Tumor volume is measured by digital caliper, and mice are weighed 3 times a week. The study ends after mice reach a predetermined endpoint (e.g. tumor volume of 3.38 cm3). At terminus, blood is collected, and tumors are harvested.

Alternative Protocols

Our Xenograft Service is entirely customizable:

We can use in-house or customer-provided cell lines.

We can begin testing a compound immediately after injecting mice with tumor cells (unstaged) or once the tumors reach a certain size (staged).

We can assign mice to groups randomly or stratify them by body weight, tumor size, disease factors, or any combination of parameters.

We can administer test compounds by any of the following methods: topically, IP, IV, SC, PO, high pressure tail vein, osmotic minipumps (SC or IP), SC drug pellets, or in the food or water.

We can snap freeze harvested tumors or fix them for histology or other specialized assays.

We can analyze blood chemistry at various times throughout the study.

Results and Analysis

When the study is complete, we analyze the data and provide you with a results summary that includes the following information:

Estimated tumor volume (L x W2 /2)

Mean/median time to specified tumor volume

Survival time to specified tumor volume

Tumor doubling time

Tumor growth inhibition (TGI)

Tumor growth delay (TGD)

Increased life span (ILS)

Tumor cell kill rate

For more information about our Xenograft Service, please contact JAX® Services at 1-800-422-6423 or 1-207-288-5845, or e-mail jaxservices@jax.org.

Table 2. Some of the human tumor cell lines maintained at The Jackson Laboratory.